Jefferson, Ohio State Team Find Gene Signature Profile for Metastasis
A
common signature of tiny, specific pieces of non-coding genetic
material known as microRNAs (miRNAs) may be directly involved in the
spread of cancer to other parts of the body. Researchers at the Kimmel
Cancer Center at Jefferson in Philadelphia and Ohio State University
Medical Center in Columbus have identified such a signature, made up
mostly of overexpressed miRNAs. The findings, reported at the annual
meeting of the American Society of Clinical Oncology in Chicago, may
represent a novel diagnostic tool in characterizing gene targets in
metastatic cancer.
MiRNAs
play a number of roles in biological regulation, including development
and cell differentiation. When damaged, they can contribute to cancer
by either turning on cancer-causing genes or by inhibiting
tumor-blocking genes. The ways that MiRNAs are expressed have been used
to profile tumor types in humans.
Because
miRNAs are involved in cancer development and progression, scientists
led by Raffaele Baffa, M.D., associate professor of Urology at
Jefferson Medical College of Thomas Jefferson University and Anne
Rosenberg, M.D., clinical professor of Surgery at Jefferson Medical
College, in collaboration with a research team led by Carlo Croce,
M.D., director of Ohio State University’s human cancer genetics program
and professor and chair of the Department of Molecular Virology,
Immunology and Medical Genetics, wanted to see if there was a specific
gene signature that characterized metastasis. Using microarray
technology to test many genes at once, they compared different organs –
breast, lung, bladder and colon – to see if miRNAs were either
increased or decreased in activity. They analyzed the miRNAs in both
primary and metastatic tumors from 43 patients, including 13 breast
cancers, 10 lung cancers, 10 bladder urothelial cell cancers and 10
colon cancers.
They discovered that some miRNAs are organ-specific. “Some are increased and decreased specifically in certain organs, telling
us that these are commonly involved in the metastatic process,” says Dr. Baffa.
Because
of the ups and downs in miRNA activity, “many miRNAs that are involved
in metastasis are not necessarily specific for one organ, but rather
are related to the cell acquiring the ability to spread.” The
researchers also found a direct association between the alterations in
some miRNAs and changes in target proteins.
Many of the miRNAs that were overexpressed in primary tumors had previously been reported, he says, confirming that miRNA
signatures are useful in classifying tissue origin.
“Now we have to identify which of the miRNAs in the signature are the most important in facilitating metastasis,” Dr. Baffa
says.
Media Only Contact:
Steve Benowitz
Thomas Jefferson University Hospital
Phone: (215) 955-6300
Published: 5/30/2008